Amblyopia is the leading cause of visual impairment in children and affects approximately 3-5% of the population worldwide. The disorder causes a syndrome of monocular and binocular deficits that persist after optical correction, in the absence of observable ocular pathology. Current treatment for amblyopia is unsuccessful in 25-50% of cases and rarely restores normal binocular vision. The broad range of deficits observed in amblyopia, its different etiologies, and the individual differences in responsiveness to treatment, suggest that multiple functional defects underlie amblyopic visual impairment. This proposal aims to isolate the core deficits that underlie the spectrum of amblyopic visual impairment, develop novel testing methods that efficiently characterize such core deficits, and evaluate how these deficits are affected by current and emerging therapies. Though the list of core deficits we propose to study may not be exhaustive, and other deficits may contribute to amblyopia, developing a framework that improves methods for monocular and binocular visual assessment will facilitate diagnosis, treatment and management of amblyopia and other visual impairments. In Aim 1, we will develop and test novel methods for rapidly assessing contrast sensitivity, binocular interaction, and spatial distortion in normal and amblyopic vision at the individual leve. In Aim 2, we will quantify the dependence of broad visual pathologies observed in amblyopia on core deficits in contrast sensitivity, binocular combination, and spatial distortion. In Aim 3, we will evaluate how conventional and emerging amblyopia treatments remediate each core deficit. The overall goal of the proposed research is therefore to develop and translate state-of-the-art psychophysical methods to clinical applications. Accomplishing the proposed aims will provide new and improved methods for (1) quantifying normal and impaired monocular and binocular vision, (2) analyzing and diagnosing visual impairment, and (3) implementing customizable rehabilitation strategies for visual impairment. The eventual development of comprehensive rehabilitative therapies for amblyopia could be achieved by targeting the core deficits. Each aim addresses a goal of the NEI's National Plan for Eye and Vision Research. PUBLIC HEALTH RELEVANCE: Amblyopia, the most common cause of visual impairment in childhood, produces a syndrome of monocular and binocular visual deficits. Existing treatments for amblyopia are unsuccessful in up to 50% cases and rarely restore binocular vision. This proposal aims to isolate the core deficits that underlie the spectrum of amblyopic visual impairment, develop novel testing methods that efficiently characterize such core deficits, and evaluate how these deficits are affected by current and emerging therapies.